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Greater circulating DPP4 activity is associated with impaired flow-mediated dilatation in adults with type 2 diabetes mellitus.
Barchetta, Ilaria; Ciccarelli, Gea; Barone, Eugenio; Cimini, Flavia A; Ceccarelli, Valentina; Bertoccini, Laura; Sentinelli, Federica; Tramutola, Antonella; Del Ben, Maria; Angelico, Francesco; Baroni, Marco G; Lenzi, Andrea; Cavallo, Maria G.
Afiliación
  • Barchetta I; Department of Experimental Medicine, Sapienza University of Rome, Italy.
  • Ciccarelli G; Department of Experimental Medicine, Sapienza University of Rome, Italy.
  • Barone E; Department of Biochemical Sciences, Sapienza University of Rome, Italy.
  • Cimini FA; Department of Experimental Medicine, Sapienza University of Rome, Italy.
  • Ceccarelli V; Department of Experimental Medicine, Sapienza University of Rome, Italy.
  • Bertoccini L; Department of Experimental Medicine, Sapienza University of Rome, Italy.
  • Sentinelli F; Department of Experimental Medicine, Sapienza University of Rome, Italy.
  • Tramutola A; Department of Biochemical Sciences, Sapienza University of Rome, Italy.
  • Del Ben M; Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
  • Angelico F; Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
  • Baroni MG; Department of Experimental Medicine, Sapienza University of Rome, Italy.
  • Lenzi A; Department of Experimental Medicine, Sapienza University of Rome, Italy.
  • Cavallo MG; Department of Experimental Medicine, Sapienza University of Rome, Italy. Electronic address: gisella.cavallo@uniroma1.it.
Nutr Metab Cardiovasc Dis ; 29(10): 1087-1094, 2019 10.
Article en En | MEDLINE | ID: mdl-31431395
BACKGROUND AND AIM: Dipeptidyl peptidase 4 (DPP4) is a key enzyme involved in the regulation of the incretin system exerted by cleaving the glucagon-like peptide 1 (GLP-1); the blockage of DPP4, exerted by the antidiabetic agents DPP4-inhibitors (DPP4-I), results in greater GLP-1 concentration and improved glycaemic control. DPP4 acts also as a pro-inflammatory molecule and mediates vascular damage in experimental models. The relationship between DPP4 activity and endothelial function in diabetes has not been explored yet. Aim of this study was to investigate systemic plasma DPP4 activity in relation to endothelial function in patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: Sixty-two T2DM individuals were recruited in our Diabetes outpatient clinics, Sapienza University, Rome, Italy. All participants underwent complete clinical work-up; endothelial function was evaluated by flow-mediated dilatation (FMD) test; plasma DPP4 activity was assessed by measuring the 7-amino-4-methylcoumarin (AMC) cleavage rate from the synthetic substrate H-glycyl-prolyl-AMC and compared with DPP4 activity measured in sixty-two age-, sex-, BMI-matched non-diabetic subjects. Patients with T2DM had significantly higher DPP4 activity than non-diabetic individuals (211,466 ± 87657 vs 158,087 ± 60267 nmol/min/ml, p < 0.001); in T2DM patients, greater DPP4 activity significantly correlated with lower FMD whereas was not associated with BMI and metabolic control. Greater systemic DPP4 activity was an independent predictor of reduced FMD after adjusting for age, gender and other confounders. CONCLUSIONS: Circulating DPP4 activity is increased in individuals with T2DM and associated with signs of endothelial dysfunction such as impaired FMD. DPP4 may negatively affect endothelial function through mechanisms beyond glucose homeostasis and metabolic control.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vasodilatación / Arteria Braquial / Endotelio Vascular / Dipeptidil Peptidasa 4 / Diabetes Mellitus Tipo 2 Tipo de estudio: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: Nutr Metab Cardiovasc Dis Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA / CIENCIAS DA NUTRICAO / METABOLISMO Año: 2019 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vasodilatación / Arteria Braquial / Endotelio Vascular / Dipeptidil Peptidasa 4 / Diabetes Mellitus Tipo 2 Tipo de estudio: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: Nutr Metab Cardiovasc Dis Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA / CIENCIAS DA NUTRICAO / METABOLISMO Año: 2019 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Países Bajos